Sodium-glucose co-transporter-2 inhibitors (SGLT-2i) are newly approved class of oral anti-diabetic drugs, in the treatment of type 2 diabetes, which reduces blood glucose through glucouresis via the kidney, independent, and irrespective of available pancreatic beta-cells. Studies conducted across their clinical development program found, a modest reduction in glycated hemoglobin ranging from −0.5 to −0.8%, without any significant hypoglycemia. Moreover, head-to-head studies versus active comparators yielded comparable efficacy. Interestingly, weight and blood pressure reduction were additionally observed, which was not only consistent but significantly superior to active comparators, including metformin, sulfonylureas, and dipeptydylpeptide-4 inhibitors. Indeed, these additional properties makes this class a promising oral anti-diabetic drug. Surprisingly, a potentially fatal unwanted side effect of diabetic ketoacidosis has been noted with its widespread use, albeit rarely. Nevertheless, this has created a passé among the clinicians. This review is an attempt to pool those ketosis data emerging with SGLT-2i, and put a perspective on its implicated mechanism.

Diabetes mellitus (DM) frequency is a growing problem worldwide, because of long life expectancy and life style modifications. In old age (≥60–65 years old), DM is becoming an alarming public health problem in developed and even in developing countries as for some authors one from two old persons are diabetic or prediabetic and for others 8 from 10 old persons have some dysglycemia. DM complications and co-morbidities are more frequent in old diabetics compared to their young counterparts. The most frequent are cardiovascular diseases due to old age and to precocious atherosclerosis specific to DM and the most bothersome are visual and cognitive impairments, especially Alzheimer disease and other kind of dementia. Alzheimer disease seems to share the same risk factors as DM, which means insulin resistance due to lack of physical activity and eating disorders. Visual and physical handicaps, depression, and memory troubles are a barrier to care for DM treatment. For this, old diabetics are now classified into two main categories as fit and independent old people able to take any available medication, exactly as their young or middle age counterparts, and fragile or frail persons for whom physical activity, healthy diet, and medical treatment should be individualized according to the presence or lack of cognitive impairment and other co-morbidities. In the last category, the fundamental rule is "go slowly and individualize" to avoid interaction with poly medicated elder persons and fatal iatrogenic hypoglycemias in those treated with sulfonylureas or insulin.

Introduction: Approximately, 33% patients with diabetes are afflicted with onychomycosis. In the past, nondermatophyte molds have been regarded as opportunistic pathogens; recently, Aspergillus species are considered as emerging pathogens of toenail infections. In Sri Lanka, the prevalence of Aspergillus species in onychomycosis among diabetics is not well documented. Objective: To determine the proportion of Aspergillus onychomycosis, risk factors and knowledge among diabetics. Materials and Methods: This was descriptive cross-sectional study. Three hundred diabetic patients were included. Clinical examinations of patients' toenails were performed by a clinical microbiologist. Laboratory identification was done, and pathogens were identified to the species level by morpho-physiological methods. All inferential statistics were tested at P < 0.05. Results: Among clinically suspected patients, 85% (255/300) were mycologically confirmed to have onychomycosis. Aspergillus species were most commonly isolated n = 180 (71%) followed by dermatophytes, yeasts, and other molds n = 75 (29%). Of the patients having Aspergillus onychomycosis, 149 (83%) were in the > age group. In men, Aspergillus onycomycosis was seen in 82%. Among patients who had Aspergillus nail infection, 114 (63%) had diabetes for a period of > years. Among patients who were engaged in agricultural activities, 77% were confirmed to have infected nails due to Aspergillus species. Conclusion:Aspergillus niger was the most common pathogen isolated from toenail infection. Aspergillus species should be considered as an important pathogen in toenail onychomycosis in diabetic patients. Risk factors associated with Aspergillus onychomycosis were age, gender, duration of diabetes, length of exposure to fungi, and occupation.

Introduction: The International Association of Diabetes in Pregnancy Study Group (IADPSG) criteria for gestational diabetes mellitus (GDM) has been adopted by most associations across the world including the American Diabetes Association and World Health Organization (WHO). We conducted a study comparing the IADPSG and previous WHO criteria and their effects on neonatal birth weight. Methods: The study was carried out in Obstetrics and Gynaecology Department of a tertiary care institute in South India in collaboration with Endocrinology Department. Thousand two hundred and thirty-one antenatal cases with at least one risk factor for GDM and gestational age of more than 24 weeks were included in the study. Both criteria were compared on the basis of 75 g oral glucose tolerance test results. Results: The prevalence of GDM using IADPSG and previous WHO criteria were 12.6% and 12.4%, respectively. The prevalence of GDM was 9.9% when both criteria had to be satisfied. Both GDM criteria groups did not differ in neonatal birth weight and macrosomia rate. However, there was a significant increase in lower segment cesarean section in IADPSG criteria group. Elevated fasting plasma glucose alone picked up only one GDM in the previous WHO criteria group. Conclusions: A single 2 h plasma glucose is both easy to perform and economical. A revised WHO criterion using a 2 h threshold of ≥140 mg % can be adopted as a one-step screening and diagnostic procedure for GDM in our country.

Objective: To determine the prevalence of celiac disease (CD) in children with type 1 diabetes mellitus (TIDM) in follow-up in a Tertiary Care Referral Centre in Western India and to describe the clinical features indicative of CD in screened patients of TIDM. Study Design: In this single center observational cross-sectional study, 71 children who were diagnosed with TIDM were subjected to screening for CD with tissue transglutaminase antibody testing. Those who tested positive were offered intestinal biopsy for the confirmation of diagnosis. Clinical profiles of both groups of patients were compared and manifestations of CD were delineated. Results: The study revealed the prevalence of CD (based on serology) in children with Type 1 diabetes as 15.49%. The prevalence of biopsy-confirmed CD was 7.04%. Of the diagnosed CD patients, one-third were symptomatic at the time of screening while the majority was asymptomatic. The major clinical features indicative of CD were intestinal symptoms, anemia, rickets, and short stature. Autoimmune thyroid disease was prevalent in 29.6% of the patients with TIDM followed by CD. Conclusions: The high prevalence of CD in children with Type 1 diabetes emphasizes the need for routine screening programs to be in place for these high-risk populations. The clinical profile of patients with CD further elaborates the indicators of CD and the need to screen for them.

Objective: To determine the best anthropometric measurement of obesity, and its optimal cutoff, that best predicts the presence of cardiovascular risk factors among adult Egyptian population. Methods: This is a cross-sectional study including a representative randomly chosen sample of the adult Egyptian population from all Alexandria Districts (the second largest governorate in Egypt) based on the multistage random technique. It included 3209 subjects (1567 men, 1642 women) aged 18–80 years from urban and rural areas. The response rate was 80.2%. History, blood pressure, and anthropometric measurements were taken. Laboratory investigations included fasting lipid profile, fasting plasma glucose, and serum uric acid. Different criteria of metabolic syndrome were used and compared. Receiver operator characteristic curve and Youden index were used to determine predictability and cutoffs. Results: Waist circumference (WC) is the best to predict at least two other components of the metabolic syndrome as defined by the International Diabetes Federation (IDF). The optimal WC cutoffs were 100.5 and 96.25 cm for Egyptian men and women, respectively. The Joint Interim Statement definition (JIS) of metabolic syndrome was the best to predict cardiovascular disease in both genders and diabetes mellitus in women. The prevalence of metabolic syndrome and abdominal obesity was 42.5%, 61%, respectively (ATPIII definition); 43.8%, 61% (American Heart Association definition); 44.3%, 76.4% (IDF definition); 33.8%, 51.7% (IDF definition with Egyptian cutoffs); and 41.5%, 51.7% (JIS with Egyptian cutoffs). Conclusion: WC cutoffs in Egyptians differ from those currently recommended. Prevalence of metabolic syndrome and abdominal obesity is high in Egypt, despite being lower on using the Egyptian cutoffs.

Diabetes is a chronic and costly disease. In India, the usual practice among patients is to visit the doctor once in every 2–3 months to get advice on changes in the dosages of medications. The Diabetes Tele Management System (DTMS®) is a telemedicine based follow-up program originally introduced at Jothydev's Diabetes Research Centre at Trivandrum South India in 1998. It is a chronic disease management system which enables patient to interact lively with a professionally trained multidisciplinary team comprising of diabetes educators, nurses, dieticians, pharmacists, psychologists, physicians, etc., in modifying the dosages of medications, diet, and physical activity either through telephone/email/secure website. The uniquely designed software and the trained multidisciplinary team overcomes the globally recognized major barriers to diabetes management namely fear of hypoglycemia, polypharmacy, discontinuation of stains, and antihypertensives or wrong injection techniques. DTMS is designed to provide individualized therapy advices on glycosylated hemoglobin, blood pressure, and low density lipoprotein customized to multiple patient characteristics which help attain goals of therapy. The system has been tested on various platforms over a decade and was shown to be a patient friendly approach with successful outcomes due to a live "round-the-clock" interactive communication in contrast to text or recorded messages. The major challenge to the widespread use of DTMS® is seeking a source of funding this unique telemedicine program.

Several studies over the past decade have now consistently indicated that the serum anti-Mullerian hormone (AMH) levels are at least 2–3-fold higher in the patients with polycystic ovary syndrome (PCOS), which also corresponds to the increased number of AMH producing preantral and small antral follicles. Moreover, AMH levels have been found to be associated in direct proportion to the follicle numbers per ovary or antral follicular count, assessed by the transvaginal ultrasound (TVS). Furthermore, AMH correlates directly with the rising serum testosterone and luteinizing hormone levels in PCOS. Hence, serum AMH in women with oligo-anovulation and/or hyperandrogenemia could indicate the presence of underlying PCOS, when reliable TVS is not feasible, or not acceptable, either due to the virginal status or psycho-social issue. In addition, the imaging quality of abdominal ultrasound is often impaired by obesity, which typically occurs in PCOS women. Indeed, PCOS occurs most commonly in young females who cannot be subjected to invasive TVS for various reasons; therefore, a desirable alternative to TVS is urgently required to diagnose the most prevalent endocrine abnormality of young women. This review will analyze the currently available evidence regarding the role of AMH in the diagnosis of PCOS.

There is an increasing deliberation regarding hypopituitarism following traumatic brain injury (TBI) and recent data have suggested that pituitary dysfunction is very common among survivors of patients having moderate-severe TBI which may evolve or resolve over time. Due to high prevalence of pituitary dysfunction after moderate-severe TBI and its association with increased morbidity and poor recovery and the fact that it can be easily treated with hormone replacement, it has been suggested that early detection and treatment is necessary to prevent long-term neurological consequences. The cause of pituitary dysfunction after TBI is still not well understood, but evidence suggests few possible primary and secondary causes. Results of recent studies focusing on the incidence of hypopituitarism in the acute and chronic phases after TBI are varied in terms of severity and time of occurrence. Although the literature available does not show consistent values and there is difference in study parameters and diagnostic tests used, it is clear that pituitary dysfunction is very common after moderate to severe TBI and patients should be carefully monitored. The exact timing of development cannot be predicted but has suggested regular assessment of pituitary function up to 1 year after TBI. In this narrative review, we aim to explore the current evidence available regarding the incidence of pituitary dysfunction in acute and chronic phase post-TBI and recommendations for screening and follow-up in these patients. We will also focus light over areas in this field worthy of further investigation.

This brief communication proposes various indices of epidemicity and endemicity which may be used to predict the future prevalence of hypothyroidism. Taking advantage of knowledge related to the natural progression of autoimmune thyroid disease, it uses data from two recent Indian epidemiological studies to assess the epidemicity or endemicity of thyroid disease in the country. The hypothesis generated in this communication will be of help to clinicians as well as policy makers.

Objective: To evaluate the efficacy and safety of canagliflozin in combination therapy among patients with type 2 diabetes mellitus with inadequate glycemic control. Methods: Two review authors independently searched for the relevant randomized controlled clinical trials from the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, IndMed, LILACS, and clinical trials registry www.clinicaltrials.gov. Primary outcomes for this review included: change in hemoglobin A1c (HbA1c) levels, fasting plasma glucose (FPG) levels and risk of occurrence of genital mycotic infections at 26 weeks. We combined results using mean difference (MD) for continuous data, and risk ratio (RR) for dichotomous data. Results: Of the 124 identified reports, five RCTs with 3565 participants were eligible for the meta-analysis. All included studies had compared canagliflozin 100 mg and 300 mg once daily with placebo or sitagliptin 100 mg once daily. We judged that most of the studies had low risk of bias or unclear risk of bias in five major domains. Canagliflozin 300 mg once daily led to a significant decrease in HbA1c levels (IV Fixed -0.77, 95% CI [-0.90, -0.64] P < 0.00001) and FPG levels (IV Fixed -2.08; 95% CI [-2.32, -1.84], P <0.00001), body weight, systolic blood pressure and triglyceride levels after 26 weeks as compared to placebo. There was a also a significant difference in the efficacy of canagliflozin 300 mg and sitagliptin 100 mg once daily in favour of canagliflozin. Both doses of canagliflozin led to genital mycotic infections among males and females, urinary tract infections, pollakiuria, polyuria and postural dizziness. Conclusions: Canagliflozin significantly decreases HbA1c and FPG levels and body weight as compared to placebo among patients with inadequate glycemic control with an earlier regime of glucose lowering agents. Long term safety studies are required to evaluate the incidence of adverse events.

Background: Pituitary adenomas (PAs) are abnormal benign tumors that develop in the pituitary gland. This study aimed to assess the prevalence of different types of PAs with an indication for trans-sphenoidal surgery in a well-defined population referred to Loghman Hakim Hospital during 2001–2013. Subjects and Methods: In this retrospective study, the prevalence rate and symptoms associated with pituitary mass and hormone excess in operated patients were investigated. The diagnosis was verified after retrieval of clinical, hormonal, radiological, and pathological data. Demographic data were collected in all cases. Descriptive analysis, t-test, one-way analysis of variance and Fischer exacts test were used. Results: A total of 278 patients with PAs who underwent surgical interventions were evaluated. Most of the patients were aged 40–50 years with an average of 41 ± 14. The most prominent complaint was pressure effect, which was detected in 153 cases (55.2%). At the second place, hormonal disorders were observed in 125 cases (44.8%). Type of pituitary tumors were: Prolactinomas (29.1%), growth hormone (GH)-producing tumors (25%), nonfunctioning PAs (28.4%), adrenocorticotropic hormone (ACTH)-producing tumors (2.1%), thyroid stimulating hormone (TSH)-producing tumors (0.7%), GH/prolactin (13.6%), GH/ACTH (0.3%), and TSH/ACTH (0.3%). Fifty-seven patients presented with recurrent adenomas. Pituitary apoplexy was found in 11 patients. One case of Sheehan syndrome was recorded among these. The correlations between clinical symptoms and patients, age and sex were not significant. Conclusion: The overview of demographic characteristics in Iranian patients with PAs with surgical indication has been discussed in the present investigation. The prevalence of different types of PAs and the most common clinical symptoms have been demonstrated.

Endocrinology is a relatively newer field in medicine but it has gained tremendous progress in the recent past and is currently one of the most cherished and sought after superspecialty subject. The journey is long and an average of 12 years is spent to complete a superspecialty training starting from Bachelor of Medicine, Bachelor of Surgery career. To get a seat in endocrinology in institutes like PGIMER, Chandigarh is difficult, the training is grueling and the final exit is tough but the vast clinical experience, research oriented teaching and the team work of the closely knit family of faculty members and resident colleagues had made these 3 years of our life as the most enjoyable years to be remembered forever.

This letter aims to bring out a few highlights and the experiences of the participants, audience, quizmasters, and the judges at Endocrine Society of India Torrent Young Scholar Award East Zonal round 2015 held in Kolkata on 6th September, 2015.

Aim: To evaluate the effect of hypothyroidism (both overt and subclinical) on cognitive function using latencies of P300 auditory evoked potentials (AEPs). P300 latency suggests that shorter latency times are related to better cognitive performance. P300 latencies were also done after thyroxine replacement to see the effect of treatment on cognitive function. Materials and Methods: Biochemically proven new onset cases with hypothyroidism (overt and subclinical) were enrolled into the study, AEPs of these two groups when compared with matched controls. After detailed history and physical examination, P300 potentials were recorded at two points Cz and Pz (Cz: On the midline of the head at the vertex, Pz: On the midline of the head between the vertex and occipital protuberance) using a Nicolet Viking Select neuro diagnostic system version 10.0. The study was done in electrophysiology lab in Osmania Medical College. Results: A patient characteristics of both cases and controls were comparable. The cases consisted of two groups, overt hypothyroid cases 24, mean thyroid stimulating hormone (TSH) values in them was 94, subclinical cases 21 in whom mean TSH value was 12.3. Mean P300 latencies of all cases at Cz was 342.42 ± 29.5 ms, and at Pz was 345.4 ± 30 ms. Mean P300 latencies of controls at Cz was 296.4 ± 34 ms and at Pz was 297.9 ± 33 ms (difference in P < 0.001). Mean P300 values in overt cases were 362.6 ± 32.9 ms at Cz, and at Pz it was 362.5 ± 33.9 ms. Mean P300 values in subclinical cases were 319.3 ± 30.9 ms at Cz, and at Pz it was 316.4 ± 27.9 ms. P300 values in overt cases were highly significant as compared to controls, and P300 values in the subclinical cases versus controls were also significant (P < 0.001). Conclusion: P300 latency prolongation in both clinical and subclinical hypothyroid cases shows that cognitive function is affected adversely in hypothyroidism including the subclinical hypothyroid cases. Larger studies evaluating the effect of subclinical hypothyroidism on cognitive function are needed with objective means such as the AEPs P300.

Aim: To assess the outcome of patients undergoing bilateral adrenalectomy for Cushing's syndrome (CS). Methods: All patients who underwent bilateral adrenalectomy for CS at the Department of Endocrine Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences hospital between 1991 and 2013 were included. Medical records were reviewed to obtain patient characteristics and follow-up data. Results: Twenty-seven patients were studied. Mean age was 28.74 ± 12.95 years (range 9–60), male:female ratio was 1.7:1. About half that is, 48.19% were of Cushing's disease (failed trans-sphenoidal surgery [TSS]), 37.04% were of ectopic CS (ECS), and 14.81% were of CS due to bilateral adrenal pathology. Median follow-up period was 80.5 months. Before surgery, 74.1% patients had body mass index > which after surgery declined to <25 in 75% of them. Hypertension was present in 85.2% and after surgery resolved in 40%. Diabetes mellitus was present in 44.4% and after surgery resolved in 33% of them. Hirsutism and proximal muscle weakness were present in 55.6% and 70.4% patients, respectively, and after surgery improved markedly in all patients. Adrenal crisis developed in 36.3% and Nelson's syndrome in 41.7% patients during follow-up. Three patients died in perioperative period while three succumbed to the disease during follow-up. Two patients developed recurrence of endogenous cortisol production during the follow-up period. Conclusions: Bilateral adrenalectomy is a valid treatment option for palliating severe symptoms in Pituitary Cushing's with failed TSS and unlocalized ECS but the procedure is curative for CS due to bilateral adrenal disease. Overall morbidity and mortality is higher than other endocrine operations. Co-morbidities tend to be more severe and are a risk factor for mortality during the time patient survives.

Prevalence of thyroid dysfunction among young females in a South Indian populationKumaravel Velayutham, S Sivan Arul Selvan, AG UnnikrishnanNovember-December 2015, 19(6):781-784DOI:10.4103/2230-8210.167546 PMID:26693428

Background: Thyroid disorders are common in India but scarce data exists on its prevalence in young women. Materials and Methods: This study was conducted in female college students in seven colleges in Madurai District, Tamil Nadu. Thyroid-stimulating hormone (TSH) was used as the screening test to diagnose thyroid dysfunction. The abnormal TSH values were classified as mild TSH elevation (TSH 4.5–10 mIU/ml), significant TSH elevation (TSH > 10 mIU/ml), and low TSH (TSH < 0.4 mIU/ml). Results: A total of 1292 subjects were screened of whom 161 subjects (12.5%) had abnormal TSH. The overall prevalence of elevated TSH was 11% out of which 9.7% had mild TSH elevation. A low TSH was seen in 1.5% of the study population. Conclusion: Thyroid dysfunction was common in young women in south India. One out of every eight young women had thyroid dysfunction, and mild TSH elevation was the most common abnormality.

Background: Our pilot data showed an increased intima media thickness in the patients with sporadic idiopathic hypoparathyroidism (SIH). Alteration in homeostasis of calcium, phosphate, and parathyroid hormone (PTH) may predispose to increase the risk of cardiovascular morbidity and mortality. The data on objective assessment of this increased risk is however lacking. Objective: To assess the effect of altered calcium, phosphate, and PTH homeostasis in the patients with SIH on coronary calcium score (a marker of increase vascular risk) by multidetector computed tomography scan (MDCT). Methods: In this case-control study, we measured coronary CT calcium score in 30 patients of SIH and compared with 40 age and sex matched healthy subjects. Correlation of coronary calcium score with biochemical parameters was evaluated. Results: Three of the 30 cases (10%) with SIH were found to have coronary artery calcification (CAC) of varying degree, whereas none of the control showed CAC (P = 0.07). The patients with CAC had significantly lower serum calcium levels (albumin corrected), as compared to the patients without CAC. Inverse correlation of CAC was found with serum calcium levels. No correlation was found with other biochemical parameters. Conclusion: The vascular risk is increased in the patients with SIH as assessed by coronary calcium score measured by MDCT. Low serum calcium levels might be a predisposing factor for this increased risk.

Objective: Growth hormone through insulin-like growth factor 1 (IGF-1) plays an important role in both bone growth and mineralization. This cross-sectional study was carried out to evaluate the relationship between serum IGF-1 concentrations and dual energy X-ray (DXA) measured whole body less head bone area (BA), lean body mass (LBM), and bone mineral content (BMC). Methods: One hundred and nineteen children (boys = 70, age = 7.3–15.6 years) were studied for their anthropometric parameters by standard methods and bone and body composition by DXA. Their fasting serum IGF-1 concentrations were assessed by enzyme-linked immunosorbent assay and Z-scores were calculated using available reference data. Bone and body composition parameter Z-scores were calculated using ethnic reference data. Results: Mean age of the boys and girls was similar (11.5 ± 1.8 years). The mean serum IGF-1concentrations and IGF-1 Z-scores were similar (P > 0.1) between boys and girls and were of the order of (302.3 ± 140.0 and − 1.4 ± 1.1, respectively). The LBM for age and BA for age Z-score was greater in children with IGF-1 Z-score > median than children with IGF-1 Z-score < median. The mean BMC for age Z-scores were 0.4 ± 0.9 and − 0.2 ± 0.8 in children with above and below the median of IGF-1 Z-score (P > 0.1). Conclusion: Serum IGF-1 levels were more strongly associated with BA and LBM, suggesting that its effect on bone is greater with respect to periosteal bone acquisition and through its effect on muscle mass.